The role of the adaptor molecule MyD88 in the immunological mechanisms induced by BCG during immunotherap against Cancer

• Grant number: 23/06778-5
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: October 01, 2023
• End date: May 31, 2027
• Field of knowledge: Biological Sciences - Immunology - Applied Immunology
• Principal Investigator: Sergio Costa Oliveira
• Grantee: Vinícius Martins Borges
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

BCG (Bacillus of Calmette-Guérin) immunotherapy has been applied for more than 40 years in non-muscle invasive bladder cancer treatment, although the mechanism of action involved in its antitumor effect is still poorly understood. The therapeutic approach on BCG use is modulate the tumor microenvironment (TME), turning cold tumors in hot tumors. Our research group have demonstrated some immune mechanisms related to intratumoral BCG effect on subcutaneous tumor model of MB49 bladder cancer and B16-F10 melanoma using several knockout (KO) mice. Taken together, in all KO animals evaluated, only MyD88-/-, Rag-/- and IFN-³-/- mice did not show complete tumor regression in response to BCG treatment compared to C57BL/6 animals, highlighting the importance of MyD88 signaling, mature lymphocytes involvement and Th1 response profile in tumor control. The adaptor molecule MyD88 has a role on macrophage and lymphocyte activation as described on literature; however, the relationship between the intrinsic MyD88 signaling on these cells and BCG antitumor effect needs elucidation. The aim of this study is evaluate the MyD88-dependent cellular components and innate and adaptive immune mechanisms of BCG immunotherapy using conditional MyD88 KO mice on macrophages, CD4+ and CD8+ T cells after subcutaneously implanted with bladder cancer (MB49) or melanoma (B16-F10) tumor. A better understanding of MyD88 signaling related to BCG response can further clarify the mechanisms of this immunotherapy and may imply in future improvements for the treatment and its possible application in different types of cancer. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

BORGES, VINICIUS M.; MARINHO, FABIO V.; CALDEIRA, CHRISTIANE V. A.; DE QUEIROZ, NINA M. G. P.; OLIVEIRA, SERGIO C.. Bacillus Calmette-Guérin immunotherapy induces an efficient antitumor response to control murine melanoma depending on MyD88 signaling. FRONTIERS IN IMMUNOLOGY, v. 15, p. 15-pg., 2024-05-21. (23/02577-5, 17/24832-6, 23/06778-5)